Doctors often rely on two pieces of diagnostic testing information when making recommendations regarding angioplasty or surgical bypass to treat coronary artery blockage: How severely a coronary artery is narrowed by plaque (plaque is a build-up of cells, cholesterol, and debris), and how much reduction in blood flow to the heart muscle ("myocardial hypoperfusion") is caused by this narrowing.1 There is evidence showing that even severely blocked coronary arteries frequently do not produce significant myocardial hypoperfusion,2 indicating that processes other than blockage severity are at work. One possible contributing process handicaps the normal ability of the coronary artery to dilate in response to blood flow. Triggers for this process also create certain changes in plaque appearance (termed "adverse features") visible on coronary computed tomographic angiography (CCTA)3-11 - a noninvasive, low-risk test that directly images coronary arterial plaque. The objective of this project is to evaluate whether finding adverse features in plaques causing severe blockage increases the patient's chances of having significant myocardial hypoperfusion. Our hypothesis is that finding any adverse plaque feature by CCTA will predict greater myocardial hypoperfusion. We will study 56 non-diabetic patients who have just been diagnosed with severe coronary artery blockage on CCTA and will be proceeding to catheter-based coronary angiography for possible angioplasty. Plaque findings on CCTA will separate the population into 2 groups: 28 will show no adverse features, and 28 will show at least 1 adverse feature. Prior to catheter-based angiography, each patient will undergo heart imaging with positron-emission tomography to measure blood flow to the heart muscle supplied by the affected coronary artery at rest and during medication-induced "stress". At the time of catheter-based angiography, each patient will undergo direct measurement of fluid pressure drop caused by the plaque. Positron-emission tomography results and pressure drop measurements will be compared between the 2 patient groups to determine the relationship between presence of adverse features and myocardial hypoperfusion. Performance of this project is intended to expand the current understanding of how to identify important coronary artery blockages, explore why certain plaques cause more myocardial hypoperfusion than others, and improve both clinical and research use of CCTA. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE (RELEVANCE) In the treatment of severe chronic coronary artery disease, the greatest benefit for angioplasty and surgical bypass are in patients whose atherosclerotic plaque build-up causes significant limitation of blood flow to the heart muscle. Although reduced blood flow is often assumed when coronary artery blockage is severe, many severe blockages do not actually cause demonstrable blood flow limitation, and the reason is not known. One potential explanation is the amount of damage to the arterial wall, which can handicap the coronary artery's ability to maintain blood flow. This project will evaluate whether certain changes in plaque appearance related to arterial wall injury, as detected by a noninvasive and safe coronary artery scan, enhance the identification of coronary artery blockages that cause significant reduction in blood flow. Improving our understanding of this relationship will help direct future efforts in researching mechanisms that cause reduced blood flow to the heart muscle and increase the efficiency of diagnostic testing for patients with coronary artery disease.